Recent incarceration and risk of hepatitis C and HIV transmission amongst people who inject drugs: A systematic review and meta-analysis Jack Stone, Hannah Fraser, Aaron Lim, Josephine Walker, Louis MacGregor, Adam Trickey, Samuel Abbott, Zoe Ward, Matthew Hickman, Peter Vickerman Population Health Sciences, Bristol Medical School, University of Bristol

Declaration No conflicts of interest to declare.

Introduction

Incarceration of People Who Inject Drugs. Globally, an estimated 58% PWID have ever been incarcerated 1 History of incarceration frequently associated with prevalent HCV and HIV infection amongst PWID 2 High risk of mortality and drug-related death in the first few weeks after release 3 [1] Degenhardt Lancet Global Health 2017 [2] Jurgens J Int. AIDS Soc. 2011 [3] Merrall Addiction 2010

Post-Release: A Period of elevated HCV and HIV risk for PWID? Studies of Community PWID have shown that recent incarceration is associated with: Increased injecting risk 1-5 Homelessness 5,6 Relapse to injecting drug use 7 Reduced intervention coverage 5,8 History of ever incarceration has also been associated with increased injecting risk behaviour 1. Injecting risk includes frequency of injecting, syringe sharing, public injecting, shooting gallery attendance. [1] Altice Lancet 2016; [2] Milloy Drug and Alcohol Review 2008; [3] Milloy BMC Pub. Health 2009; [4] Westergaard Clin Infect Dis. 2011; [5] Unpublished Analyses for Scotland. [6] Topp J Urb Health 2013; [7] Genberg Addiction 2015. [8] Koehn Addict Behav 2015.

Objectives Perform a systematic review and meta-analyses to quantify the associations between: A history of ever incarceration and HIV acquisition risk amongst community PWID. A history of recent incarceration and HIV acquisition risk amongst community PWID. A history of ever incarceration and HCV acquisition risk amongst community PWID. A history of recent incarceration and HCV acquisition risk amongst community PWID.

Methods

Search Strategy Search terms included those related to HIV infection or transmission; HCV infection or transmission; intravenous drug use; and study designs that could be used to evaluate HIV or HCV incidence. MEDLINE, Embase and PsycINFO databases Searches were limited to those published since 2000. No limitation on language. Search updated on the 13th June 2017 Reference lists of potentially relevant systematic reviews were hand- searched for relevant papers/reports Authors of identified HIV and HCV incidence studies that met the inclusion criteria but did not report on the outcomes of interest were contacted for additional data.

Inclusion & Exclusion Criteria Include studies of active PWID or those with history of injecting Exclude studies set in prisons or similar locations of detention Exclude studies that evaluated incident infections by self- report Include only studies reporting original results Include all study designs including cross-sectional studies that utilised biological markers of recent HIV or HCV infections to estimate incidence.

Data Analysis Unadjusted and adjusted relative risks based on HRs, IRRs and ORs were extracted or derived from data. ORs were transformed to RRs when HCV or HIV incidence were high (>10 per 100py) 1 Effect measures and standard errors were log-transformed and pooled using random effects meta-analysis. Between-study heterogeneity was evaluated using the I2 statistic and the P value for heterogeneity 2 We performed subgroup analyses and random-effects meta-regression analyses to explore potential sources of heterogeneity. We assessed the risk of bias of each study for each included outcome using the Newcastle-Ottawa Scale We assessed publication bias by comparing unpublished and published estimates. Random effects meta-analysis because we expected heterogeneity between studies. [1] Zhang JAMA 1998 [2] Huedo-Medina Psychological methods 2006

Results

Selection of Studies 42809 citations identified by database search MEDLINE (16760) Embase (21811) PsycINFO (4238) 25434 screened after duplicates removed 25086 excluded 348 full texts screened for eligibility 48 studies included in quantitative synthesis: 12 HIV, ever incarceration 14 HIV, recent incarceration 21 HCV, ever incarceration 18 HCV, recent incarceration 308 full text articles excluded: 49 review/editorial/letter 12 Not PWID 247 No outcome of interest 28 Unpublished estimates Selection of Studies 68 studies with relevant data 20 Duplicate Data

Ever Incarceration and HIV Acquisition Risk 12 studies. 9 unpublished; 3 published Overall (I2=50.9%, p=0.022) 1.25 (0.94,1.66) Increases Risk Decreases Risk

Recent Incarceration and HIV Acquisition Risk 14 studies. 10 unpublished. 4 published. Overall (I2=63.5%, p=0.001) 1.81 (1.40,2.34) Increases Risk Decreases Risk

Ever Incarceration and HCV Acquisition Risk 21 studies. 10 unpublished. 11 published. Overall (I2=45.4%, p=0.013) 1.25 (1.06,1.48) Increases Risk Decreases Risk

Recent Incarceration and HCV Acquisition Risk 17 studies. 10 unpublished. 7 published. Overall (I2=57.3%, p=0.002) 1.62 (1.28,2.05) Increases Risk Decreases Risk

Sensitivity Analyses Ever incarceration & risk of HIV acquisition Recent incarceration & risk of HIV acquisition Ever incarceration & risk of HCV acquisition Recent incarceration & risk of HCV acquisition Crude estimates RR: 1.25 (0.94-1.66) n=12 RR: 1.81 (1.40-2.34) n=14 RR: 1.25 (1.06-1.48) n=21 RR: 1.62 (1.28-2.05) n=17 Adjusted estimates Longitudinal studies only Studies with >90% injecting in last 6 months Studies with Low/Medium Risk of Bias Published estimates Unpublished Estimates

Sensitivity Analyses Ever incarceration & risk of HIV acquisition Recent incarceration & risk of HIV acquisition Ever incarceration & risk of HCV acquisition Recent incarceration & risk of HCV acquisition Crude estimates RR: 1.25 (0.94-1.66) n=12 RR: 1.81 (1.40-2.34) n=14 RR: 1.25 (1.06-1.48) n=21 RR: 1.62 (1.28-2.05) n=17 Adjusted estimates RR: 1.24 (0.55-2.80) n=2 RR: 1.54 (1.13-2.09) n=5 RR: 1.12 (0.88-1.42) n=6 RR: 1.60 (1.21-2.11) n=11 Longitudinal studies only Studies with >90% injecting in last 6 months Studies with Low/Medium Risk of Bias Published estimates Unpublished Estimates

Sensitivity Analyses Ever incarceration & risk of HIV acquisition Recent incarceration & risk of HIV acquisition Ever incarceration & risk of HCV acquisition Recent incarceration & risk of HCV acquisition Crude estimates RR: 1.25 (0.94-1.66) n=12 RR: 1.81 (1.40-2.34) n=14 RR: 1.25 (1.06-1.48) n=21 RR: 1.62 (1.28-2.05) n=17 Adjusted estimates RR: 1.24 (0.55-2.80) n=2 RR: 1.54 (1.13-2.09) n=5 RR: 1.12 (0.88-1.42) n=6 RR: 1.60 (1.21-2.11) n=11 Longitudinal studies only RR: 1.15 (0.67-1.64) n=10 RR: 1.79 (1.36-2.36) RR: 1.23 (1.01-1.50) n=18 RR: 1.59 (1.22-2.08) Studies with >90% injecting in last 6 months Studies with Low/Medium Risk of Bias Published estimates Unpublished Estimates

Sensitivity Analyses Ever incarceration & risk of HIV acquisition Recent incarceration & risk of HIV acquisition Ever incarceration & risk of HCV acquisition Recent incarceration & risk of HCV acquisition Crude estimates RR: 1.25 (0.94-1.66) n=12 RR: 1.81 (1.40-2.34) n=14 RR: 1.25 (1.06-1.48) n=21 RR: 1.62 (1.28-2.05) n=17 Adjusted estimates RR: 1.24 (0.55-2.80) n=2 RR: 1.54 (1.13-2.09) n=5 RR: 1.12 (0.88-1.42) n=6 RR: 1.60 (1.21-2.11) n=11 Longitudinal studies only RR: 1.15 (0.67-1.64) n=10 RR: 1.79 (1.36-2.36) RR: 1.23 (1.01-1.50) n=18 RR: 1.59 (1.22-2.08) Studies with >90% injecting in last 6 months RR: 0.96 (0.63-1.48) RR: 1.76 (1.47-2.12) n=8 RR: 1.10 (0.84-1.43) n=7 RR: 1.55 (1.11-2.15) Studies with Low/Medium Risk of Bias Published estimates Unpublished Estimates

Sensitivity Analyses Ever incarceration & risk of HIV acquisition Recent incarceration & risk of HIV acquisition Ever incarceration & risk of HCV acquisition Recent incarceration & risk of HCV acquisition Crude estimates RR: 1.25 (0.94-1.66) n=12 RR: 1.81 (1.40-2.34) n=14 RR: 1.25 (1.06-1.48) n=21 RR: 1.62 (1.28-2.05) n=17 Adjusted estimates RR: 1.24 (0.55-2.80) n=2 RR: 1.54 (1.13-2.09) n=5 RR: 1.12 (0.88-1.42) n=6 RR: 1.60 (1.21-2.11) n=11 Longitudinal studies only RR: 1.15 (0.67-1.64) n=10 RR: 1.79 (1.36-2.36) RR: 1.23 (1.01-1.50) n=18 RR: 1.59 (1.22-2.08) Studies with >90% injecting in last 6 months RR: 0.96 (0.63-1.48) RR: 1.76 (1.47-2.12) n=8 RR: 1.10 (0.84-1.43) n=7 RR: 1.55 (1.11-2.15) Studies with Low/Medium Risk of Bias RR: 1.19 (0.82-1.73) RR: 1.75 (1.30-2.35) RR: 0.99 (0.77-1.28) n=9 RR; 1.68 (1.23-2.29) Published estimates Unpublished Estimates

Sensitivity Analyses Ever incarceration & risk of HIV acquisition Recent incarceration & risk of HIV acquisition Ever incarceration & risk of HCV acquisition Recent incarceration & risk of HCV acquisition Crude estimates RR: 1.25 (0.94-1.66) n=12 RR: 1.81 (1.40-2.34) n=14 RR: 1.25 (1.06-1.48) n=21 RR: 1.62 (1.28-2.05) n=17 Adjusted estimates RR: 1.24 (0.55-2.80) n=2 RR: 1.54 (1.13-2.09) n=5 RR: 1.12 (0.88-1.42) n=6 RR: 1.60 (1.21-2.11) n=11 Longitudinal studies only RR: 1.15 (0.67-1.64) n=10 RR: 1.79 (1.36-2.36) RR: 1.23 (1.01-1.50) n=18 RR: 1.59 (1.22-2.08) Studies with >90% injecting in last 6 months RR: 0.96 (0.63-1.48) RR: 1.76 (1.47-2.12) n=8 RR: 1.10 (0.84-1.43) n=7 RR: 1.55 (1.11-2.15) Studies with Low/Medium Risk of Bias RR: 1.19 (0.82-1.73) RR: 1.75 (1.30-2.35) RR: 0.99 (0.77-1.28) n=9 RR; 1.68 (1.23-2.29) Published estimates n=3 RR: 2.59 (1.91-3.52) n=4 RR: 1.39 (1.11-1.74) RR: 1.58 (1.02-2.45) Unpublished Estimates RR: 1.00 (0.73-1.38) RR: 1.47 (1.14-1.90) RR: 1.10 (0.88-1.37) RR: 1.61 (1.22-2.12)

Meta-Regression Results No effect of geographical region, country-level income, study type or effect type on estimates. Lower effect of ever and possibly recent incarceration on HIV acquisition risk if higher proportion of females (for ever per 10% increase; Ratio of RR: 0.77 (0.64-0.93), P=0.011, n=11) Greater effect of recent incarceration on HCV acquisition risk in countries with larger prison populations1: Ratio of RR: 1.72 (1.04- 2.82), P=0.035, n=17). Lower effect of recent incarceration on HIV acquisition risk in studies with older participants at the start of the study2 (Ratio of RR: 0.54 (0.34-0.87), P=0.016, n=13). Greater effect of recent incarceration on HCV acquisition risk in studies with more homelessness at baseline3: Ratio of RR 2.21 (1.63-2.99), P=0.016, n=8). In Multivariate regression, 1 High prison population rate defined as above global average: 144 per 100,000. 2 >=33.6 years vs <33.6 years 3 >=42.8% vs <42.8%

Conclusions

Discussion Recent incarceration is associated with a 81% and 62% increase in the risk of HIV and HCV acquisition amongst PWID, respectively. Strong effect of recent incarceration preserved in sensitivity analyses. Ever incarceration is only weakly associated with increased risk of HIV and HCV acquisition. Meta-regression suggests Homelessness may be on causal pathway or act in synergy with incarceration. Higher rates of incarceration may increase the effects of incarceration.

Implications Need to investigate the mechanisms through which incarceration elevates HCV and HIV acquisition risk amongst PWID Prison-based OST associated with retention following release 1-3 But evidence of effect of recent incarceration in Scotland, where prison- based OST coverage is high (57%) 4 Likely that prison-based harm reduction with linkage on release and structural interventions required to reduce the risks associated with incarceration With high incarceration rates amongst PWID, incarceration is likely to be a significant contributor to the HIV and HCV epidemics amongst PWID Our findings add to the growing body of evidence of the harms associated with international drug policy 5 and support the need for reform. [1] Marsden Addiction 2017; [3] Hedrich Addiction 2012 [3] Wickersham Drug Alcohol Depend 2013 [4] Taylor Addiction 2013; [5] Csete lancet 2016.

Acknowledgements Hannah Fraser Malvina Aladashvili Ellen Heinsbroek Aaron Lim Viktor Mravčík Ross Harris Josephine Walker Michel Alary Sharon Hutchinson Louis MacGregor Elise Roy Norah Palmateer Adam Trickey Pavlo Smyrnov Andy McAuley Samuel Abbott Yana Sazonova Lucy Platt Zoe Ward April Young Natasha Martin Steffanie Strathdee Jennifer Havens Frederick Altice Daniela Abramovitz Vivian Hope Matthew Hickman Lisa Maher Monica Desai Peter Vickerman Jenny Iversen Richard Garfein Yung-Fen Yen Tasnim Azim Shruti Mehta Thomas Kerr Margaret Hellard Rachel Sacks-Davis

Scotland Modeling Study A third. 6% 45% Stone et al. " Modelling the impact of incarceration and prison-based hepatitis C virus (HCV) treatment on HCV transmission among people who inject drugs in Scotland” Addiction 2017

Ukraine Modeling Study Altice et al. "The perfect storm: incarceration and the high-risk environment perpetuating transmission of HIV, hepatitis C virus, and tuberculosis in Eastern Europe and Central Asia." The Lancet 388.10050 (2016): 1228-1248.